ROLE OF TH2 CELLS IN EOTAXIN REGULATION

TH2 细胞在嗜酸细胞趋化因子调节中的作用

• 批准号: 6536731
• 负责人: ANUJA MATHEW
• 金额: $ 4.62万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6536731
• 关键词: asthma; biological signal transduction; cell cell interaction; chemokine; clone cells; disease /disorder model; electroporation; eosinophil; epithelium; gel mobility shift assay; gene expression; genetically modified animals; helper T lymphocyte; interleukin 1; interleukin 13; interleukin 4; interleukin 5; interleukin 9; laboratory mouse; messenger RNA; monocyte; nuclear factor kappa beta; protein biosynthesis; protein protein interaction; protein structure function; reporter genes; site directed mutagenesis; tissue /cell culture; transcription factor; tumor necrosis factor alpha

Asthma is a disease of airway inflammation in which airway eosinophilia is a prominent histologic feature. Eosinophils can release toxic mediators, lipids and pro-inflammatory cytokines that can induce airway hyper- responsiveness. Identifying the mechanisms that are involved in recruiting eosinophils to the site of injury are therefore critical in the understanding of pathogenesis of disease. Chemokines are a family of secreted proteins that play a critical role in directing different types of leukocytes to the site of infection of tissue damage. The aim of this proposal is to examine the role of Th2 cells in regulating the expression of eotaxin, a chemokine specific for eosinophils. We hope to identify and characterize molecules or factors released from Th2 cells that are responsible for affecting the expression of eotaxin at the mRNA and protein levels. We then hope to identify transcription factors that are important in promoting gene expression of eotaxin. The importance of these molecules will be examined in vivo using existing knockout animals. This work will lead to the greater understanding of the role of Th2 cells and eotaxin asthma.

哮喘是一种气道炎症疾病，其中气道嗜酸性粒细胞增多是一个突出的组织学特征。嗜酸性粒细胞可以释放有毒介质、脂质和促炎细胞因子，从而诱发气道高反应性。因此，确定将嗜酸性粒细胞募集到损伤部位的机制对于理解疾病的发病机制至关重要。趋化因子是一类分泌蛋白，在引导不同类型的白细胞到达组织损伤感染部位方面发挥着关键作用。该提案的目的是检查 Th2 细胞在调节嗜酸性粒细胞趋化因子（一种嗜酸性粒细胞特异性趋化因子）表达中的作用。我们希望鉴定和表征 Th2 细胞释放的分子或因子，这些分子或因子负责在 mRNA 和蛋白质水平上影响嗜酸细胞趋化因子的表达。然后我们希望鉴定出对于促进嗜酸细胞趋化因子基因表达很重要的转录因子。这些分子的重要性将使用现有的基因敲除动物进行体内检查。这项工作将有助于更好地了解 Th2 细胞和嗜酸细胞趋化因子哮喘的作用。